The Molecular Biology Core Facility (Core A) is a shared resource that provides and integrates a number of related molecular biology an biochemistry services for six of the seven individual research projects of the proposed Dartmouth SBRP Program. The overall goal of this core is to provide needed molecular biology services in a low-cost, timely and high quality manner, using existing and pendular state-of-the-art equipment and full-time technical personnel in a central institutionally supported facility, and to provide high level technical expertise and advice to individual projects and advice to individual projects. The Specific Aims of this core are to 1) provide macromolecular (DNA, RNA, peptides, proteins) sequencing and synthesis services including standard and custom oligonucleotide synthesis; automated cycle DNA sequencing and synthesis services including standard and custom oligonucleotide synthesis automated cycle DNA sequencing, peptide synthesis and purification, automated protein sequencing; LCQ-Mass spectral analysis of macromolecules; and HPLC and PCR support services; 2) provide image generation and analysis services including phosphorimaging, digital densitometry and analysis; x-ray film processing; and flow cytometry; and 3) provide support for development of molecular biomarkers including differential display analysis, ribonuclease protection assay analysis; Affymetrix-based cDNA/ gene "chip" technology; user- generated custom cDNA array capabilities; cloning and sequencing support for newly identified sequences; support for computer-based sequence analysis; genetic polymorphism analysis; method development for potential protein and nucleic acid-based biomarkers for application in ecological and epidemiological trials as well as for further hypothesis testing in the more basic research projects. Support for this core is seen as vital and central to the overall goals and success of this program project.